The proposal is focused on the identification of genetic elements controlling MIs-1 superantigen expression. Because MIs-1 expression is critical for successful transmission of infectious Murine Mammary Tumor Virus (MMTV), it is important to understand the control of expression of this molecule. We will progress from our preliminary data indicating that MMTV superantigen gene (sag) transcription is regulated independently of that of the other MMTV genes. First, using nested deletions in reporter gene constructs and transients expression assays, we will map a promoter element identified in a subclone of the Mtv-7 env gene. We will continue to investigate the relevance of the octamer sites in the 5' and 3' Mtv- 7LTR for B cell specific expression, and the role of the LTR glucocorticoid responsive elements in MIs-l expression. The results will be confirmed by testing for functional MIs-l expression in stable transfectants. Also, the in vivo relevance of the identified transcriptional elements will be tested using the first cloned infectious MMTV which has an identical sag gene as Mtv-7. Elucidating the mechanisms of the expression of MIs-1 will help establish the functional relevance of superantigens for pathogen and host, and may open new approaches for therapeutics and prevention of viral infection.